American Geriatrics Society and National Institute on Aging Bench-to-Bedside conference: sensory impairment and cognitive decline in older adults

This article summarizes the presentations and recommendations of the tenth annual American Geriatrics Society and National Institute on Aging Bench‐to‐Bedside research conference, “Sensory Impairment and Cognitive Decline,” on October 2–3, 2017, in Bethesda, Maryland. The risk of impairment in hearing, vision, and other senses increases with age, and almost 15% of individuals aged 70 and older have dementia. As the number of older adults increases, sensory and cognitive impairments will affect a growing proportion of the population. To limit its scope, this conference focused on sensory impairments affecting vision and hearing. Comorbid vision, hearing, and cognitive impairments in older adults are more common than would be expected by chance alone, suggesting that some common mechanisms might affect these neurological systems. This workshop explored the mechanisms and consequences of comorbid vision, hearing, and cognitive impairment in older adults; effects of sensory loss on the aging brain; and bench‐to‐bedside innovations and research opportunities. Presenters and participants identified many research gaps and questions; the top priorities fell into 3 themes: mechanisms, measurement, and interventions. The workshop delineated specific research questions that provide opportunities to improve outcomes in this growing population.Funding was provided by National Institutes of Health (NIH) Grant U13 AG054139-01. Dr. Whitson's efforts and contributions were supported by R01AG043438, R24AG045050, UH2AG056925, and 5P30AG028716. Dr. Lin's effort and contributions were also supported by R01AG055426, R01HL096812, and R33DC015062. (U13 AG054139-01 - National Institutes of Health (NIH); R01AG043438; R24AG045050; UH2AG056925; 5P30AG028716; R01AG055426; R01HL096812; R33DC015062)Accepted manuscrip

Age-related neurochemical changes in the rhesus macaque inferior colliculus

Age-related hearing loss (ARHL) is marked by audiometric hearing deficits that propagate along the auditory pathway. Neurochemical changes as a function of aging have also been identified in neurons along the auditory pathway in both rodents and carnivores, however, very little is known about how these neurochemicals change in the non-human primate. To examine how these compensatory neurochemical changes relate to normal aging and audiometric sensitivity along the auditory pathway, we collected auditory brainstem responses (ABRs) and brain specimens from seven rhesus monkeys spanning in age from 15 to 35 years old, and examined the relationship between click evoked ABR thresholds and the ABR evoked pure tone average (PTA) and changes in the number of parvalbumin and NADPH-diaphorase positive cells in the auditory midbrain. We found that the number of parvalbumin positive cells in the central nucleus and the surrounding cortex regions of the inferior colliculus were strongly correlated with advancing age and ABR PTA. We also found that the numbers of NADPHd positive cells in these same regions were not associated with normal aging or changes in the ABR thresholds. These findings suggest that the auditory midbrain undergoes an up-regulation of parvalbumin expressing neurons with aging that is related to changes in the processing of frequencies across the audiometric range

Heschl's gyrus is more sensitive to tone level than non-primary auditory cortex

Previous neuroimaging studies generally demonstrate a growth in the cortical response with an increase in sound level. However, the details of the shape and topographic location of such growth remain largely unknown. One limiting methodological factor has been the relatively sparse sampling of sound intensities. Additionally, most studies have either analysed the entire auditory cortex without differentiating primary and non-primary regions or have limited their analyses to Heschl's gyrus (HG). Here, we characterise the pattern of responses to a 300-Hz tone presented in 6-dB steps from 42 to 96 dB sound pressure level as a function of its sound level, within three anatomically defined auditory areas; the primary area, on HG, and two non-primary areas, consisting of a small area lateral to the axis of HG (the anterior lateral area, ALA) and the posterior part of auditory cortex (the planum temporale, PT). Extent and magnitude of auditory activation increased non-linearly with sound level. In HG, the extent and magnitude were more sensitive to increasing level than in ALA and PT. Thus, HG appears to have a larger involvement in sound-level processing than does ALA or PT

Interaction of perceptual grouping and crossmodal temporal capture in tactile apparent-motion

Previous studies have shown that in tasks requiring participants to report the direction of apparent motion, task-irrelevant mono-beeps can "capture'' visual motion perception when the beeps occur temporally close to the visual stimuli. However, the contributions of the relative timing of multimodal events and the event structure, modulating uni- and/or crossmodal perceptual grouping, remain unclear. To examine this question and extend the investigation to the tactile modality, the current experiments presented tactile two-tap apparent-motion streams, with an SOA of 400 ms between successive, left-/right-hand middle-finger taps, accompanied by task-irrelevant, non-spatial auditory stimuli. The streams were shown for 90 seconds, and participants' task was to continuously report the perceived (left-or rightward) direction of tactile motion. In Experiment 1, each tactile stimulus was paired with an auditory beep, though odd-numbered taps were paired with an asynchronous beep, with audiotactile SOAs ranging from -75 ms to 75 ms. Perceived direction of tactile motion varied systematically with audiotactile SOA, indicative of a temporal-capture effect. In Experiment 2, two audiotactile SOAs-one short (75 ms), one long (325 ms)-were compared. The long-SOA condition preserved the crossmodal event structure (so the temporal-capture dynamics should have been similar to that in Experiment 1), but both beeps now occurred temporally close to the taps on one side (even-numbered taps). The two SOAs were found to produce opposite modulations of apparent motion, indicative of an influence of crossmodal grouping. In Experiment 3, only odd-numbered, but not even-numbered, taps were paired with auditory beeps. This abolished the temporal-capture effect and, instead, a dominant percept of apparent motion from the audiotactile side to the tactile-only side was observed independently of the SOA variation. These findings suggest that asymmetric crossmodal grouping leads to an attentional modulation of apparent motion, which inhibits crossmodal temporal-capture effects

Music training alters the course of adolescent auditory development

Fundamental changes in brain structure and function during adolescence are well characterized, but the extent to which experience modulates adolescent neurodevelopment are not. Musical experience provides an ideal case for examining this question because the influence of music training begun early in life is well known. We investigated the effects of in-school music training, previously shown to enhance auditory skills, versus another in-school training program that did not focus on development of auditory skills (active control). We tested adolescents on neural responses to sound and language skills before they entered high school (pre-training) and again three years later. Here we show that in-school music training begun in high school prolongs the stability of subcortical sound processing and accelerates maturation of cortical auditory responses. Although phonological processing improved in both the music training and active control groups, the enhancement was greater in adolescents who underwent music training. Thus, music training initiated as late as adolescence can enhance neural processing of sound and confer benefits for language skills. These results establish the potential for experience-driven brain plasticity during adolescence, and demonstrate that in-school programs can engender these changes

Distortions of Subjective Time Perception Within and Across Senses

Background: The ability to estimate the passage of time is of fundamental importance for perceptual and cognitive processes. One experience of time is the perception of duration, which is not isomorphic to physical duration and can be distorted by a number of factors. Yet, the critical features generating these perceptual shifts in subjective duration are not understood. Methodology/Findings: We used prospective duration judgments within and across sensory modalities to examine the effect of stimulus predictability and feature change on the perception of duration. First, we found robust distortions of perceived duration in auditory, visual and auditory-visual presentations despite the predictability of the feature changes in the stimuli. For example, a looming disc embedded in a series of steady discs led to time dilation, whereas a steady disc embedded in a series of looming discs led to time compression. Second, we addressed whether visual (auditory) inputs could alter the perception of duration of auditory (visual) inputs. When participants were presented with incongruent audio-visual stimuli, the perceived duration of auditory events could be shortened or lengthened by the presence of conflicting visual information; however, the perceived duration of visual events was seldom distorted by the presence of auditory information and was never perceived shorter than their actual durations. Conclusions/Significance: These results support the existence of multisensory interactions in the perception of duration and, importantly, suggest that vision can modify auditory temporal perception in a pure timing task. Insofar as distortions in subjective duration can neither be accounted for by the unpredictability of an auditory, visual or auditory-visual event, we propose that it is the intrinsic features of the stimulus that critically affect subjective time distortions

Repetitive afferent electrical stimulation of the lower-limb : effect on corticomotor excitability and implications for rehabilitation

Despite the extensive work published on the effects of electrical stimulation on corticomotor excitability, very few studies have focused on lower limb muscles. The aim of the present study was to determine the effect of high-frequency afferent electrical stimulation of the anterior thigh area on the corticomotor excitability of lower limb muscles. Twenty-two healthy subjects (mean age 23 ± 7 yrs) participated in the study. Electrical stimulation was applied for 60 minutes on the anterior thigh area (frequency 100 Hz, pulse duration 60 µs, intensity below motor threshold). Motor evoked potentials (MEP) of the rectus femoris and biceps femoris muscles were recorded before, and after the electrical stimulation paradigm with a Magstim 200 stimulator. Analyses revealed a significant modulation in MEP amplitude for the RF but not for the BF muscle. Specifically, there was a significant reduction in MEP amplitude for the RF muscle immediately, 15 minutes and 30 minutes after the end of electrical stimulation when compared with baseline. The present results indicate that a 60-minute high-frequency electrical stimulation protocol applied on the anterior thigh area decreases the corticomotor excitability of the RF muscle. Although the exact duration remains unknown, the pattern of modulation observed indicates that the inhibitory effect lasts for more than 30 minutes after the end of stimulation, giving enough time for clinicians to work on the desired motor task during rehabilitation

Integrating incremental learning and episodic memory models of the hippocampal region.

By integrating previous computational models of corticohippocampal function, the authors develop and test a unified theory of the neural substrates of familiarity, recollection, and classical conditioning. This approach integrates models from 2 traditions of hippocampal modeling, those of episodic memory and incremental learning, by drawing on an earlier mathematical model of conditioning, SOP (A. Wagner, 1981). The model describes how a familiarity signal may arise from parahippocampal cortices, giving a novel explanation for the finding that the neural response to a stimulus in these regions decreases with increasing stimulus familiarity. Recollection is ascribed to the hippocampus proper. It is shown how the properties of episodic representations in the neocortex, parahippocampal gyrus, and hippocampus proper may explain phenomena in classical conditioning. The model reproduces the effects of hippocampal, septal, and broad hippocampal region lesions on contextual modulation of classical conditioning, blocking, learned irrelevance, and latent inhibition

Influence of Audiovisual Training on Horizontal Sound Localization and Its Related ERP Response

The objective was to investigate the influence of audiovisual training on horizontal sound localization and the underlying neurological mechanisms using a combination of psychoacoustic and electrophysiological (i.e., event-related potential, ERP) measurements on sound localization. Audiovisual stimuli were used in the training group, whilst the control group was trained using auditory stimuli only. Training sessions were undertaken once per day for three consecutive days. Sound localization accuracy was evaluated daily after training, using psychoacoustic tests. ERP responses were measured on the first and last day of tasks. Sound localization was significantly improved in the audiovisual training group when compared to the control group. Moreover, a significantly greater reduction in front-back confusion ratio for both trained and untrained angles was found between pre- and post-test in the audiovisual training group. ERP measurement showed a decrease in N1 amplitude and an increase in P2 amplitude in both groups. However, changes in late components were only found in the audiovisual training group, with an increase in P400 amplitude and decrease in N500 amplitude. These results suggest that the interactive effect of audiovisual localization training is likely to be mediated at a relatively late cognitive processing stage